tbuckley/cabot-search huggingface dataset:
Abstract P3-04-07: Safety and artifact testing of a nitinol breast biopsy clip in an ultra-high resolution magnetic resonance imaging (MRI) environment
Authors: William Dong, Kanchna Ramchandran, Adam Galloy, Marco A. Nino, Marla Kleingartner, Madhavan L. Raghavan, Sneha Phadke, Vincent A. Magnotta
Journal: Cancer Research (2023)

Abstract Background: The lack of safety clearance of several metallic breast implants in 7T(Tesla) poses a significant hurdle to standard clinical breast cancer care and research from reaping the benefits of ultra-high resolution MR imaging. A breast biopsy clip (Ultracor Twirl, Becton, Dickinson and Company, Vernon Hills, IL) composed of nitinol, was tested for safety and artifact susceptibility clearance in a 7T MRI scanner, using standardized procedures. This clearance is significant in henceforth allowing patients with this implant to be scanned in now FDA approved ultra-high-field MRI scanners of 7T or less for clinical and research purposes. Methods: Tests for magnetic susceptibility (torque and translational attraction), MRI-related heating, and artifacts were conducted as per standardized protocols. The torque and translational attraction tests evaluated the effects of magnetic force by the MRI to cause the clip to move and twist respectively. The heating test was conducted with customized MR parameters of short TR (repetition time) and maximum echo-train length, designed to induce temperature change. The artifact test using T1 weighted spin and gradient echo imaging sequences, evaluated potential localized signal loss that may result in misrepresentation of the imaged area. This may occur due to the presence of the metallic clip in the MR environment. Results: The torque and translational attraction tests respectively indicated that the MR environment did not induce any movement in the clip in eight orientations, with a deflection angle of 0 degrees. Results of the heating test indicated no significant temperature change of the clip. A temperature change of less than 0.45C° was observed in the phantom gel in both the absence and presence of the clip, which is well within the safety threshold (&amp;lt; 1°C). Results of the artifact test indicated a very small artifact, with the largest artifact cross-sectional area appearing on gradient echo images. Conclusion: These cumulative results indicate that the Ultracor Twirl breast biopsy clip is safe for imaging patients at 7T. Citation Format: William Dong, Kanchna Ramchandran, Adam Galloy, Marco A. Nino, Marla Kleingartner, Madhavan L. Raghavan, Sneha Phadke, Vincent A. Magnotta. Safety and artifact testing of a nitinol breast biopsy clip in an ultra-high resolution magnetic resonance imaging (MRI) environment [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-04-07.
Abstract P5-14-07: Somatic mutations of ER and HER2 subtypes exhibit divergent evolutionary trajectories determined by selective epistasis revealed in phylogenetic reconstruction and stage-specific analyses
Authors: Krishna Dasari, J. Nick Fisk, Jeffrey Townsend
Journal: Cancer Research (2023)

Abstract Estrogen-receptor positive (ER+) and human epidermal growth factor receptor positive (HER2+) subtypes of breast cancers feature distinct histopathologies and prognoses. Their molecular profiles inform subtype-specific treatment combinations and possible therapeutic targets. However, the evolutionary trajectory of somatic mutations within each subtype has not been characterized, despite its utility in prioritizing drug development and therapeutic approaches. Quantifying the selective effects of somatic mutations on cancer conveys the likely efficacy of extant targeted therapies between subtypes. Furthermore, knowledge of epistatic interactions involving targetable mutations enables precision therapy at any stage of tumorigenesis. The strength of these interactions differ between receptor subtypes, mediated by differences in the adaptive landscape of each subtype. To investigate differences in subtype etiologies, we quantified selection on single-nucleotide mutations within ER and HER2 receptor subtypes using an aggregated multi-institutional cohort of tumor samples. We observed differential selection acting on mutations: PIK3CA H1047R is a strongly selected variant for which selection varied significantly based on the receptor subtype, experiencing maximal selection in ER+ HER2﹣ breast cancer. On a stage-specific basis, we show that adaptive landscapes change, altering optimal timings for treatment. We then infer epistasis by 1) stage-specific analysis that suggests likely orderings of mutations, 2) calculation of pairwise selective epistasis amongst mutations, which lends mechanistic explanations to these orderings, and 3) phylogenetic reconstruction of the evolution of ten breast cancers, revealing common orderings that further support inferred selective epistatic interactions. Our estimates of differential and stage-specific selection and epistasis between subtypes suggest distinct adaptive landscapes for breast cancer subtypes. These estimates should inform the development of targeted therapeutics and guide treatment schedules based on molecular profiling of the cancer. Citation Format: Krishna Dasari, J. Nick Fisk, Jeffrey Townsend. Somatic mutations of ER and HER2 subtypes exhibit divergent evolutionary trajectories determined by selective epistasis revealed in phylogenetic reconstruction and stage-specific analyses [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-14-07.
Abstract P2-11-25: A 10-gene signature to predict the prognosis of early-stage triple-negative breast cancer
Authors: Chang Min Kim, Kyong Hwa Park, Yun Suk Yu, Ju Won Kim, Jin Young Park, Jeong Eon Lee, Sung Hoon Sim, Bo Kyoung Seo, Jin Kyeoung Kim, Eun Sook Lee, Yeon Hee Park, Sun-Young Kong
Journal: Cancer Research (2023)

Abstract Background: Triple-negative breast cancer (TNBC) is highly heterogeneous cancer and the most challenging subtype of breast cancer. And its prognosis is poor compared to the other subtypes. Unlike luminal type cancers, there is no valid biomarker to predict the prognosis of patients with early TNBC. To establish an elaborate therapeutic strategy for TNBC, biomarkers that accurately predict the prognosis and response to treatment are needed. Method: 184 patients with early stage TNBC (training cohort, n = 76; validation cohort, n = 108) were enrolled. Median Follow-up period was 51.5 months (range: 4.6-230.8) for training cohort and 58.3 months (range: 6.6-99.8) for validation cohort. Of the patients in training cohort, 13 patients had recurrence or metastasis. Of the patients in validation cohort, 23 patients had recurrence or metastasis. Using a HiSeq sequencer, RNA sequencing was conducted to analyze the gene expression profiles of tumor samples from TNBC patients. Gene signature was analyzed by combination of DEGs which found in gene expression profiles. Cross validation and meta-analysis were conducted as pre-validation. Meta-analysis was conducted using CBS probePINGS. To compare gene signature and other methods, PAM 50 call and TCR diversity analysis were investigated. Statistical analyses were conducted using R language (v.3.4.3). Result: To predict prognosis of recurrence or metastasis for TNBC patients, we identified the 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3 and SLC45A4) that stratified patients with TNBC by risk score (sensitivity = 92.31%; specificity = 92.06%; accuracy = 92.11%) and validated in a cohort of separate institutions. Meta-analysis supported the biological relevance of the 10-gene signature to well-known driving pathways in TNBC. When compared with other potential biomarkers like PAM 50 call and T-cell receptor β diversity, the 10-gene signature was the only independent factor that can predict prognosis for invasive disease-free survival in multivariate analysis. Conclusion: Our novel findings can contribute to solving the diagnostic challenges in TNBC and the 10-gene signature may serve as a novel biomarker for risk-based patient care. Citation Format: Chang Min Kim, Kyong Hwa Park, Yun Suk Yu, Ju Won Kim, Jin Young Park, Jeong Eon Lee, Sung Hoon Sim, Bo Kyoung Seo, Jin Kyeoung Kim, Eun Sook Lee, Yeon Hee Park, Sun-Young Kong. A 10-gene signature to predict the prognosis of early-stage triple-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-25.
Abstract P3-05-50: Comprehensive Analysis of Pyroptotic Gene Prognostic Signatures Associated with Tumor Immune Microenvironment and Genomic Mutation in Breast Cancer
Authors: Hongfei Zhang, Xiafei Yu, Junzhe Yang, Xiaoan Liu, Yanhui Zhu
Journal: Cancer Research (2023)

Abstract Background: Breast cancer is becoming a tumor with the highest morbidity rate, and inflammation-induced cell death namely pyroptosis reportedly plays dual roles in cancers. However, the specific mechanism between pyroptosis and the clinical prognosis of breast cancer patients is indistinct. Hence, novel pyroptosis-related biomarkers and their contributing factors deserve further exploration to predict the prognosis in breast cancer. Methods: Pearson’s correlation analysis, and univariate and multivariate Cox regression analysis were utilized to obtain six optimal pyroptosis-related gene prognostic signatures (Pyro-GPS). The risk score of each breast cancer patient was calculated. Next, a Pyro-GPS risk model was constructed and verified in TCGA cohort (n=1,089) and GSE20711 cohort (n=88). Then analyses of immune microenvironment, genomic variation, functional enrichment, drug response and clinicopathologic feature stratification associated with the risk score of Pyro-GPS were performed. Ultimately, a nomogram based on the risk score and several significant clinicopathologic features was established. Results: The low-risk breast cancer patients have better survival outcomes than the high-risk patients. The low-risk patients also show higher immune cell infiltration levels and immune-oncology target expression levels. There is no significant difference in genetic variation between the two risk groups, but the frequency of gene mutations varies. Functional enrichment analysis shows that the low-risk patients are prominently correlated with immune-related pathways, whereas the high-risk patients are enriched in cell cycle, ubiquitination, mismatch repair, homologous recombination and biosynthesis-related pathways. Pyro-GPS is positively correlated with the IC50 of anti-tumor drugs. Furthermore, comprehensive analyses based on risk score and clinicopathological features were performed to predict the prognosis of breast cancer patients. Conclusions: The risk score of Pyro-GPS can serve as a promising hallmark to predict the prognosis of BRCA patients. Risk score evaluation may assist to acquire relevant information of tumor immune microenvironment, genomic mutation status, functional pathways and drug sensitivity, and thus provide more effective personalized strategies. Citation Format: Hongfei Zhang, Xiafei Yu, Junzhe Yang, Xiaoan Liu, Yanhui Zhu. Comprehensive Analysis of Pyroptotic Gene Prognostic Signatures Associated with Tumor Immune Microenvironment and Genomic Mutation in Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-50.
Abstract P4-07-19: Eribulin enhances STING-dependent induction of type I interferons in immune and triple-negative breast cancer cells
Authors: Leila Takahashi-Ruiz, Charles Fermaintt, Nancy Wilkinson, Susan Mooberry, April Risinger
Journal: Cancer Research (2023)

Abstract Triple-negative breast cancer (TNBC) is a heterogenous subtype of breast cancer that lacks effective targeted treatment options. However, TNBC typically has a higher mutational burden and greater degree of immunogenicity than other breast tumors, making immunotherapy a viable strategy for effective treatment of this disease. Strategies to improve the response of TNBC patients to immunotherapy include the upregulation of the cGAS-STING innate immune sensing pathway and STING agonists are in clinical development for the treatment of TNBC. We demonstrate that eribulin, a microtubule destabilizer currently used in the treatment of TNBC, functions as an indirect STING agonist because it promotes the release of mitochondrial DNA into the cytoplasm. Eribulin also enhances type I interferon expression induced by STING agonists through a second TBK1-dependent mechanism downstream of STING activation that is shared by the RIG/MAVS RNA sensing pathway. Both mechanisms of eribulin-mediated activation of interferon expression occur in immune and TNBC cells and are shared with other microtubule destabilizers, including vinorelbine, but not with the microtubule stabilizing agent paclitaxel. These effects of eribulin on innate immune sensing pathways in vitro prompted further evaluations of the impact of eribulin on the in vivo immunological response to mammary tumors. We found that eribulin, but not paclitaxel, promotes the activation of CD4+ T-cells in the spleens and draining lymph nodes of tumored animals. This activation required tumor priming but was independent of any direct effect on tumor growth inhibition, demonstrating a specific role of eribulin as a tumor immune modulator. These data contribute to accumulating evidence that there are important mechanistic differences between the microtubule targeted chemotherapeutics currently used in the treatment of TNBC and suggest that eribulin elicits a more favorable innate immunological signature than paclitaxel. Research supported by Eisai Inc. Citation Format: Leila Takahashi-Ruiz, Charles Fermaintt, Nancy Wilkinson, Susan Mooberry, April Risinger. Eribulin enhances STING-dependent induction of type I interferons in immune and triple-negative breast cancer cells [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-19.
Abstract P6-05-59: Clinical Characteristics and Prognosis of Postpartum Breast Cancer
Authors: Soo Youn Bae, Pill Sun Paik, Young Joo Lee, Young-Joon Kang
Journal: Cancer Research (2023)

Background: Postpartum breast cancer (PPBC) is a not well-established subset of breast cancer, and only few studies address its poorer prognosis. However, there are previous studies that PPBC is associated with worse outcome with higher rates of metastasis than in young women's breast cancer (YWBC). The purpose of this study was to analyze the clinical characteristics and prognosis according to the onset period of PPBC, Materials and methods: 208,780 breast cancer patients from the online Korean Breast Cancer Society (KBCS) registry database between January 2000 and December 2014 were reviewed retrospectively. Premenopausal women aged 20 to 50 years who underwent breast cancer surgery were included. According to the diagnosis period of breast cancer, it was classified into groups diagnosed within 5 years (PPBC< 5) after delivery, between 5-10 years((5≤PPBC< 10), and after 10 years(PPBC≥10). Results: The patients in PPBC < 5 group showed a younger and more advanced stage compared to other groups, and the expression of estrogen receptor (ER) and progesterone receptor (PR) was lower and the HER2 positive rate was higher. PPBC< 5 group had worse survival rate compared to nulliparous and other group (5-year cumulative survival; PPBC< 5 group, 89% vs. nulliparous group, 97.3% vs. 5≤ PPBC< 10 group 93%). In multivariate analysis, PPBC< 5 group was associated with worse survival rate (Hazard ratio 1.55, 95% CI 1.148-2.094, p=0.004) after adjustment for age at diagnosis, breast cancer stage, ER and HER2 status, Ki-67 level, and chemotherapy. Conclusion: We demonstrated that patients with breast cancer diagnosed within first five years after delivery had aggressive characteristics and a worse survival rate. In order to improve the survival rate of PPBC, the cause should be identified and new therapeutic strategy should be established.Citation Format: Soo Youn Bae, Pill Sun Paik, Young Joo Lee, Young-Joon Kang. Clinical Characteristics and Prognosis of Postpartum Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-59.
Abstract P4-03-44: A Case Series of Male Breast Cancer Patients at Methodist Dallas Medical Center
Authors: Huy Nong, Vasu Moparty, Atisha Manhas
Journal: Cancer Research (2023)

Abstract Male breast cancer is a rare disease accounting for less than 1% of all breast cancer diagnosis. Male breast cancers occur later in life and are more estrogen receptor-positive compared to female breast cancers. Breast cancer in men is often diagnosed later and survival rates are lower than in female cases. The aim of this retrospective study is to analyze the epidemiological, clinical and therapeutic data of all male breast cancer cases over the span of 11 years to at Methodist Dallas Medical Center between 2010 – 2021. During this time period, there was a total of 1,784 cases of breast cancer diagnosed. There were 8 cases male breast cancers, accounting for 0.45% of all breast cancer cases. The average age of diagnosis was 69.5 years old. The most common type of male breast cancer was invasive ductal carcinoma with 7 cases (87.7%). The remaining 1 case (12.5%) were ductal carcinoma in situ (DCIS). 100% of our male breast cancer cases were estrogen receptor and progesterone receptor positive. No male breast cancer case had Her2/Neu receptor over-expression. Of all male breast cancer cases, 75% had a family history of cancer suggesting that genetic factors play a significant role in the development of breast cancer in men. At time of diagnosis, 4 cases (50 %) were staged at cT4 and the remainder of cases were between cT0 - cT2. 37.5% of all cases had sentinel lymph node involvement at time of diagnosis. From the time period of 2010 – 2014 there were no incidences of male breast cancer; however, from 2015 – 2021 there were 8 total cases. There were 2 cases (25%) of death. Number of Male Breast Cancer Cases by Year Number of Male Breast Cancer Cases by Year Number of male breast cancer cases diagnosed by year at Methodist Dallas Medical Center Epidemiological and Clinical Data of Male Breast Cancer Cases Citation Format: Huy Nong, Vasu Moparty, Atisha Manhas. A Case Series of Male Breast Cancer Patients at Methodist Dallas Medical Center [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-44.
Abstract P5-01-09: Evaluation of the efficacy of using fluorescence-associated indocyanine green in sentinel lymph node biopsies from breast cancer patients
Authors: Rafael Sá, Afonso Nazário, Vanessa M. Sanvido, Roberto Giordano, Raquel Rodrigues, Luiz Bugalho, Suelen Silva
Journal: Cancer Research (2023)

Abstract Introduction: Sentinel lymph node biopsy is the technique of choice for axillary staging in patients with breast cancer. Although it is already a widespread technique, its history is relatively recent. Three techniques are globally used to detect sentinel lymph nodes: the patent blue, described by Giuliano et al. (1994); the technetium-99 radiopharmaceutical with gamma probe, published by Krag et al. (1993); and the combination of these two techniques. Objective: This study aims to evaluate sentinel lymph node detection rate using the innovative fluorescence-associated indocyanine green technique in breast cancer patients, and to compare it with that of patent blue and with a combination of the two dyes. Method: A randomized trial was conducted on 99 patients who were equally divided into three arms, each one undergoing sentinel lymph node detection using either patent blue, indocyanine green, or a combination of the two dyes. The study was conducted at Hospital de Esperança, Presidente Prudente, SP, Brazil, in partnership with the Breast Department of Paulista School of Medicine, Federal University of São Paulo. Results: The accuracy rate in identifying sentinel lymph nodes was 78.8% with patent blue, 93.9% with indocyanine green, and 100% with patent blue + indocyanine green. Two sentinel nodes (48.5%) were mostly identified in the combined group; however, only one sentinel node was identified in the other groups. The mean time for sentinel lymph node identification was 20.6 minutes with the traditional dye, 8.6 minutes with indocyanine green, and 10 minutes with the combination of the two methods (p &amp;lt; 0.001). The mean surgical time was 69.4 minutes with patent blue, 55.1 minutes with indocyanine green, and 69.4 minutes with their combination (p &amp;lt; 0.001). Conclusion: Sentinel lymph node detection rate by fluorescence-associated indocyanine green was considered effective. The comparison of sentinel lymph node detection rates between patent blue, indocyanine green, and a combination of patent blue + indocyanine green revealed statistically significant differences (p = 0.030), with the combined method being the most effective. Keywords: breast neoplasm, sentinel lymph node biopsy, fluorescence, indocyanine green Citation Format: Rafael Sá, Afonso Nazário, Vanessa M. Sanvido, Roberto Giordano, Raquel Rodrigues, Luiz Bugalho, Suelen Silva. Evaluation of the efficacy of using fluorescence-associated indocyanine green in sentinel lymph node biopsies from breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-01-09.